IP3R-Grp75-VDAC1-MCU calcium regulation axis antagonists protect podocytes from apoptosis and decrease proteinuria in an Adriamycin nephropathy rat model.

BACKGROUND: The mechanism of podocyte apoptosis is not fully understood. In addition, the role of the inositol 1,4,5-triphosphate receptor (IP3R)/glucose-regulated protein 75 (Grp75)/voltage-dependent anion channel 1 (VDAC1)/mitochondrial calcium uniporter (MCU) calcium regulation axis, which is located at sites of endoplasmic reticulum (ER) mitochondria coupling, in the mechanism of podocyte apoptosis is unclear. This study aimed to understand the roles of this axis in podocyte apoptosis and explore potential targets for podocyte protection. METHODS: The expression of IP3R, Grp75, VDAC1, and MCU and mitochondrial Ca2+ were analyzed during Adriamycin- or angiotensin II-induced apoptosis in cultured mouse podocytes. The interaction between IP3R, Grp75, and VDAC1 was investigated using co-immunoprecipitation experiments. The effects of IP3R, Grp75, and MCU agonists and antagonists on mitochondrial Ca2+ and apoptosis were investigated in cultured podocytes. The podocyte-protective effects of an MCU inhibitor were further investigated in rats with Adriamycin-induced nephropathy. RESULTS: Increased expression of IP3R, Grp75, VDAC1 and MCU, enhanced interaction among the IP3R-Grp75-VDAC1 complex, mitochondrial Ca2+ overload, and increased active caspase-3 levels were confirmed during Adriamycin- or angiotensin II-induced mouse podocyte apoptosis. Agonists of this axis facilitated mitochondrial Ca2+ overload and podocyte apoptosis, whereas specific antagonists against IP3R, Grp75, or MCU prevented mitochondrial Ca2+ overload and podocyte apoptosis. A specific MCU inhibitor prevented Adriamycin-induced proteinuria and podocyte foot process effacement in rats. CONCLUSIONS: This study identified a novel pathway in which the IP3R-Grp75-VDAC1-MCU calcium regulation axis mediated podocyte apoptosis by facilitating mitochondrial Ca2+ overload. Antagonists that inhibit Ca2+ transfer from ER to mitochondria protected mouse podocytes from apoptosis. An MCU inhibitor protected podocytes and decreased proteinuria in rats with Adriamycin-induced nephropathy. Therefore, antagonists to this pathway have promise as novel podocyte-protective drugs.

[Influence of photoselective vaporization of the prostate on the sexual function of the patient].

n recent years, photoselective vaporization of the prostate (PVP) has gained a wide clinical application in the treatment of benign prostatic hyperplasia (BPH) for its satisfactory effect, high safety, and low incidence of complications. With the improvement of living conditions, BPH patients are paying more attention to their sexual function, especially erectile function and ejaculatory problems instead of just focusing on the alleviation of lower urinary tract symptoms. Few studies of PVP, however, relate to its association with the sexual function of the patient and there is a certain controversy over the influence of PVP on it in the existing literature. Prevailing views hold that the uprated power in PVP does not affect erectile function or increase the risk of retrograde ejaculation (REj) and that PVP is even better than transurethral resection of the prostate (TURP) in avoiding the risk of REj.

[One-puncture one-needle TRUS-guided prostate biopsy for prevention of postoperative infections].

OBJECTIVE: To explore the feasibility and effectiveness of "one-puncture one-needle" transrectal ultrasound (TRUS)-guided prostate biopsy in the prevention of postoperative infections. METHODS: We retrospectively analyzed the clinical data about "one-puncture one-needle" (the observation group) and "one-person one-needle" (the control group) TRUS-guided prostate biopsy performed in the Second People's Hospital of Guangdong Province from January 2005 to December 2015, and compared the incidence rates of puncture-related infection between the two strategies. By "one-puncture one-needle", one needle was used for one biopsy puncture, while by "one-person one-needle", one needle was used for all biopsy punctures in one patient and the needle was sterilized with iodophor after each puncture. RESULTS: Totally, 120 patients received 6+1-core or 12+1-core "one-person one-needle" and 466 underwent 12+1-core "one-puncture one-needle" TRUS-guided prostate biopsy. There were no statistically significant differences between the two groups of patients in age, the prostate volume, the serum PSA level, or the detection rate of prostate cancer (P >0.05). Compared with the control group, the observation group showed remarkably lower incidence rates of puncture-related urinary tract infection (7.5% vs 0.9%, P <0.05), fever (5.0% vs 1.1%, P <0.05), bacteriuria (2.5% vs 0.2%, P <0.05), and total infections (16.7% vs 2.6%, P<0.05) postoperatively. Two cases of bacteremia or sepsis were found in each of the groups, with no significant difference between the two. CONCLUSIONS: "One-puncture one-needle" TRUS-guided prostate biopsy can effectively prevent puncture-related infections.

Determination of pesticide residues in tea by gas chromatography/triple quadrupole mass spectrometry with solid-phase extraction.

An analytical method was developed for determination of multipesticide residues, including organophosphorus, organohalogen, pyrethroid, and organonitrogen, in tea at trace levels by GC coupled with triple quadrupole mass chromatography (QqQ-MS/MS). Scan time was selected in order to optimize QqQ-MS/MS conditions. The key parameters for controlling cleanup performance were optimized, including SPE cartridge type and elution solvent volume. Acetonitrile was the extraction solvent, and a novel multilayer SPE cartridge, Cleanert TPT, was used in the cleanup step. The recoveries of the studied pesticides at 5.0, 10.0, and 25.0 microg/kg were in the range of 77.8 to 103.8% with an RSD of less than 14%. Determination coefficient (R2) values between 0.9951 and 0.9998 were obtained for all target compounds. The LOD was between 0.002 and 1.0 microg/kg, and LOQs were 0.0066-3.3 microg/kg, which satisfied the maximum residue limits for pesticides in tea recommended by the European Union and Japan. The optimized method was applied to the analysis of real tea samples obtained from the local market.

[Yimusake Tablet: safe and efficacious for premature ejaculation].

OBJECTIVE: To objectively evaluate the efficacy and safety of Yimusake Tablet in the treatment of premature ejaculation (PE) through a multi-centered large-sample trial. METHODS: We conducted a multi-centered, open, fixed-dose, and self-compared clinical trial among 300 patients with diagnosed PE. The trial lasted 12 weeks, including 4 weeks without any medication and 8 weeks of treatment with Yimusake Tablet, 2 pills (1 g) per night. We observed the intravaginal ejaculation latency time (IELT) before and after treatment, evaluated the safety of medication, and performed a questionnaire investigation on the patients' satisfaction. RESULTS: Of the 300 PE patients, 288 accomplished the clinical trial. The patients ranged in age from 22 to 60 years, averaging at 31.6 years. The mean IELT of the patient was 62.5 seconds at baseline, 168.9 seconds after 4 weeks of treatment with Yimusake Tablet, and 222.2 seconds after 8 weeks of medication. Among the 157 patients with normal erectile function (IIEF >21), the mean IELT was 71.4 seconds before treatment, 147.4 seconds after 4 weeks of medication, and 172.5 seconds after 8 weeks of medication. The patients' satisfaction was significantly increased after treatment. Those complicated by mild to moderate erectile dysfunction achieved different degrees of improvement in the IIEF-5 score, with a mean increase of 3.8. Only a few patients experienced mild adverse events, including constipation, dry mouth, nose bleeding, abdominal pain, and lumbosacral pain, which were all relieved without drug withdrawal. CONCLUSION: Yimusake Tablet is a safe and effective medicine for the treatment of PE.

Enantioseparation of four organophosphonate derivatives on N-(3,5-dinitrobenzoyl)-L-leucine-n-propylamide stationary phase by molecular modeling.

Four groups of organophosphonate derivatives enantiomers were separated on N-(3,5-dinitrobenzoyl)-S-leucine chiral stationary phase. The three-dimensional structures of the complexes between the single enantiotopic chiral compounds and chiral stationary phase have been studied using molecular model and molecular dynamics simulation. Detailed results regarding the conformation, auto-docking, and thermodynamic estimation are presented. The elution order of the enantiomer could be determined from the energy. The predicted chiral discrimination was obtained by computational results.

[Endothelial microparticles and erectile dysfunction: an update].

Microparticles are submicron vesicles shed from plasma membranes in response to cell activation, injury and/or apoptosis. Microparticles of various cellular origins, such as platelets, leukocytes, and endothelial cells, are found in the plasma of healthy subjects, and their amount increases under pathological conditions. Recent studies show that endothelial microparticles, a kind of envelope particles derived from endothelial cells, not only constitute a marker of endothelial dysfunction, but also play a major biological role in the diagnostic and therapeutic approaches to erectile dysfunction.

[Influence of photoselective vaporization of prostate on erectile function in patients with benign prostatic hyperplasia].

OBJECTIVE: To assess the influence of photoselective vaporization of the prostate (PVP) on the erectile function of the patient with benign prostatic hyperplasia (BPH). METHODS: Using IIEF-5, we conducted a questionnaire investigation among 210 BPH patients before and after treated by PVP (n = 80) and transurethral resection of the prostate (TURP, n = 130). We also reviewed the clinical data and compared the pre- and post-operative penile erectile function between the two groups of patients. RESULTS: Follow-up was completed in 76 cases of PVP and 123 of TURP. The baseline data showed no statistically significant differences between the two groups in age, prostate volume, IPSS, QOL, Qmax, post void urine residual volume and IIEF-5 scores (P>0.05). Compared with the IEFF-5 score at the baseline (21.88 +/- 2.46), those at 3, 6 and 12 months after PVP were 16.72 +/- 3.17, 19.34 +/- 2.46 and 19.29 +/- 2. 18, respectively, significantly decreased at 3 months (P = 0.042), but with no remarkable difference at 6 and 12 months (P >0.05). Nor were there significant differences in the IIEF-5 score between the PVP and TURP groups at any time points (P>0.05). At 6 months after surgery, the incidence rates of erectile dysfunction were 11.7% and 13.7% in the TURP and PVP groups, respectively (P>0.05). CONCLUSION: PVP may reduce erectile function in some cases in the early stage after surgery, but this adverse effect does not last long and is basically similar to that of TURP.

Biotransformation of Abiraterone Into Five Characteristic Metabolites by the Rat Gut Microbiota and Liver Microsomes.

It is well known that the role of gut microbiota in drug metabolism, especially in oral difficult absorbable drugs. Understanding the gut microbiota could enable us to understand drugs in new ways. The purpose of the study was to investigate explore the metabolites of the anti-prostate cancer drug Abiraterone by examining gut microbiota metabolism and hepatic metabolism in vitro. In this study, five metabolites (M1, M2, M3, M4 and M5) of Abiraterone were discovered using LC/MSn-IT-TOF. Four isomeric metabolites M1-M4 were found in liver microsome. M5 was found in the intestinal contents of Sprague-Dawley rats with a molecular weight of 388.31. Among them, M4 was found to be Abiraterone N-Oxide by comparison with the standard sample. After further comparing the metabolic behavior of Abiraterone in rat gut microbiota and liver microsomes, we delineated the possible metabolic pathways of Abiraterone. In conclusion, Abiraterone is metabolized specifically in liver microsomes and gut microbiota. This study can provide a theoretical basis for elucidating the metabolic mechanism of Abiraterone and guide its rational application in clinic.

Combined therapy with simvastatin and bone marrow-derived mesenchymal stem cells increases benefits in infarcted swine hearts.

OBJECTIVE: Widespread death of implanted cells hampers stem cell therapy for acute myocardial infarction (AMI). Based on the pleiotropic beneficial effects of statins, we examined whether simvastatin (SIMV) increased the efficacy of mesenchymal stem cell (MSC) transplantation after AMI. METHODS AND RESULTS: Chinese miniswine (n=28) were randomized to 1 of 4 groups (n=7 per group): control, SIMV (0.25 mg/kg x d), MSC transplantation, and SIMV+MSCs. AMI was created by ligating the left anterior descending coronary artery; MSCs were injected immediately into the cyanotic myocardium. At 6 weeks, MRI showed the number of dyskinetic segments and the infarct size were significantly decreased in the SIMV group. Cardiac function improved and the perfusion defect decreased significantly in the SIMV+MSC group but not in the MSC-only group (P<0.05, versus control group). MSC survival and differentiation were significantly better in the combination group than in the MSC-only group (P<0.01). Cell apoptosis decreased significantly in both the SIMV and the SIMV+MSC groups but not in the MSC-only group when compared with controls (P<0.05). Furthermore, oxidative stress and inflammatory response was significantly reduced in the infarcted regions in both the SIMV and the SIMV+MSCs groups. CONCLUSIONS: SIMV treatment improves the therapeutic efficacy of MSC transplantation in acutely infarcted hearts by promoting cell survival and cardiovascular differentiation.

[Paratesticular embryonal rhabdomyosarcoma: report of 5 cases and review of the literature].

OBJECTIVE: To improve the diagnosis and treatment of paratesticular embryonal rhabdomyosarcoma (PER). METHODS: We retrospectively studied the clinical data of 5 cases of PER treated from 1997 to 2009 and reviewed the relevant literature, focusing on its clinical manifestations, diagnosis and treatment. RESULTS: The 5 cases of PER, 2 involving the spermatic cord, 2 the testis and 1 the tunica vaginalis, were all treated by radical orchiectomy. Pathologically, 2 cases were classified as stage I, 1 as stage II and 2 as stage IV. Postoperatively, 2 of the patients received chemotherapy and the other 3 refused adjunctive therapy. The patients were followed up for 6, 12, 18 and 28 months, respectively. Four of them remained free from relapse and metastasis, and 1 stage IV patient died of multiple metastasis at 6 months. CONCLUSION: Early diagnosis, radical orchiectomy and adjunctive chemo- or radio-therapy are effective means to the treatment of PER.

Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts.

AIMS: To investigate whether Atorvastatin (Ator) treatment improves the cardiac micro-environment that facilitates survival and differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) implanted in the post-infarct myocardium. METHODS AND RESULTS: Myocardial infarction was created by coronary ligation and immediately after reperfusion, autologous bone-marrow-derived MSCs were transplanted into the hearts of Chinese swine that were pretreated with or without Ator. Six weeks after transplantation, as evaluated by SPECT and MRI all the animals with Ator showed improved cardiac perfusion and contractility when compared with untreated. Increased survival and differentiation of implanted MSCs and decreased infarct area were observed in the Ator-treated, MSC-implanted animals. In the absence of Ator, MSC transplantation only achieved a modest improvement in perfusion and morphology. The combined treatment with Ator and MSCs significantly inhibited cardiac cell apoptosis, reduced oxidative stress, and suppressed expression of the inflammatory cytokines in the post-infarct myocardium. CONCLUSION: Ator treatment may protect the myocardium undergoing acute infarction and reperfusion by creating a better environment for the survival and differentiation of implanted MSCs. The benefit of the Ator/stem cell combined therapy may result from the statin-mediated inhibition of apoptosis, oxidative stress, and inflammation in the infarcted myocardium.

No significant association between immunosuppression in solid organ transplantation and prostate cancer risk: a meta-analysis of cohort studies.

BACKGROUND: It is known that organ transplant recipients have a significantly higher risk for developing cancers, but the association between immunosuppression in organ transplantation and the risk for prostate cancer (PCa) remains unclear. We aimed to assess the evidence regarding the association of solid organ transplantation with PCa risk. METHODS: A literature search of the PubMed, Embase, and Web of Science databases was performed up to March 2019. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using a fixed-effect or random-effect model. RESULTS: In total, 26 articles including 33 independent population-based cohort studies with 556,812 recipients and 2,438 PCa cases were identified and included in this meta-analysis. PCa risk in the solid organ transplant recipients did not increase compared with the general population (RR=1.04; 95% CI: 0.90-1.18). Independent analysis of different kinds of organ replacements further indicated immune inhibition in the transplantation of kidney, liver, heart, and lung, and was not associated with elevated PCa risk (RR=0.89; 95% CI: 0.83-0.95; RR=0.61, 95% CI: 0.21-1.02; RR=1.70, 95% CI: 0.88-2.52; RR=0.87, 95% CI: 0.57-1.16, respectively). CONCLUSIONS: This study demonstrated that immunosuppression in solid organ transplant recipients was not associated with higher PCa risk.

Chlorine levels and species in fine and size resolved atmospheric particles by X-ray absorption near-edge structure spectroscopy analysis in Beijing, China.

An understanding of the species of chlorine is crucial in the metropolis-Beijing, which is suffering serious haze pollution with high frequency. Particulate Matters (PMs) with five different sizes were collected in Beijing from July 2009 to March 2016, and characterized non-destructively by X-ray absorption near edge structure spectroscopy. PM<0.2, PM0.2-0.5 and PM>2.5 contributed for the major PMs mass in spring and summer, PM0.5-1.0 and PM1.0-2.5 contributed for the major PMs mass in autumn and winter. The concentrations of the three chlorine species were in the order of inorganic chlorine (Clinorg) > aliphatic chlorine (Clali) > aromatic chlorine (Claro), indicating that Clinorg constituted the primary chlorine fraction and less toxic Clali constituted the primary total organic chlorine (Clali + Claro, abbreviated as Clorg) in the PMs in Beijing. In addition, these three chlorine species exhibited identical seasonal variation in PM2.5: winter > autumn > spring > summer. Wet precipitation is an important factor to result in the lower mass concentrations of these three chlorine species in summer. The temporal variations of both size resolved PM mass concentrations and chlorine species concentrations suggested that the air pollution prevention and control in Beijing has just won initial success.

Expression of oestrogen receptor-alpha and oestrogen receptor-beta in prostate cancer.

BACKGROUND: Recent studies have suggested that estrogens are involved in normal and abnormal prostate growth, though their exact role is still controversial. Oestrogens exert inhibitory and stimulatory effects on prostate gland, but the expression of oestrogen receptor-alpha (ERalpha) and oestrogen receptor-beta (ERbeta) in malignant prostate tissue remains unresolved. We determined ERalpha and ERbeta in prostate cancer and investigated the relationship between expression of ER and pathological features of prostate carcinoma. METHODS: Thirty-two cases of prostate cancer, 12 cases of normal prostate tissue and 32 cases of benign prostate hyperplasia were analyzed for the expression of ERalpha and ERbeta using semiquantitative, reverse transcription polymerase chain reaction (RT-PCR) and the products sequenced. RESULTS: Comparisons of the normal, hyperplastic and tumour prostate tissues indicated an overexpression of ERalpha in tumour specimens (P < 0.01). However, the expression of ERbeta significantly reduced in tumour tissues compared with normal and hyperplastic specimens (P < 0.01), suggesting that severe pathological features of prostate cancer were associated with lower ERbeta expression. Spearman analysis showed negative correlation between ERbeta expression and tumour stage, grade (-0.67, -0.43, respectively, both P < 0.05), and a positive correlation between ERalpha expression and tumour stage, grade (0.51, 0.57, respectively, both P < 0.01). Our analysis also showed that hormone refractory, prostate cancer, compared with hormone dependent, prostate cancer, displayed a decreased expression of ERbeta (P < 0.01) and an increased expression of ERalpha. CONCLUSIONS: ERalpha and ERbeta may play important roles in the development of prostate cancer. The decrease in ERbeta expression is associated with higher Gleason grade tumours and prostate cancer with higher metastatic potential. The loss of ERbeta could be one of the key processes leading to uncontrolled growth of prostate epithelial cells.

Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts.

BACKGROUND: Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion. METHODS: Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. RESULTS: At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL. CONCLUSIONS: Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.

[Study on anti-tumor effect of dry and fresh Gekko swinhonis freeze-dried powders on mice sarcoma S180 and acute toxicity testing of two powders].

OBJECTIVE: To investigate the anti-tumor activity of dry Gekko swinhonis freeze-dried powder (DGFP) and fresh G. swinhonis freeze-dried powder (FGFP) on mice sarcoma S180 and acute toxicity testing of the two powders. METHOD: Mice xenotransplant model of sarcoma S180 was established. Eighty mice were randomly divided into 8 groups. Control group were orally administrated by saline, another intraperitoneally injected with 5-Fu, the other six groups were orally administrated by DGFP and FGFP, each at three different doses (low, moderate and high). Rate of restraining tumor, index of thymus and spleen were calculated after 10 days' treatment. Acute toxicity testing tried to figure out LDs and LD, of DGFP and FGFP. RESULT: The restraining tumor rates of DGFP and FGFP each at three doses were 31.4%, 50.8%, 37.7% and 14.8%, 19.1%, 54.7%. DGFP and FGFP elevated the thymic weight and thymic index of the mice to different extent. There were no significant differences among the eight groups in their spleen weight and spleen index. Acute toxicity testing did not figure out LD50 of DGFP and FGFP. In LD0 test, the administrating dosages of DGFP and FGFP given to the mice were both more than 2000 times than those given to patients on clinic. The result showed nothing abnormal in DGFP group. Compared with the DGFP and control group there was only a significant body weight decrease (P < 0.01) in the FGFP group in the first three days. However, on the fifth day and the seventh day there was no significant difference. CONCLUSION: DGFP and FGFP have conspicuous anti-tumor effects in vivo. The mechanism may be related to the elevated cellular immune function. Acute toxicity testing reveals that DGFP and FGFP are quite safe for conventional oral use on clinic.

Effect of cocaine on germ cell apoptosis in rats at different ages.

AIM: To investigate the effect of cocaine on apoptosis and caspase-3 activity in germ cells in male rats at different ages. METHODS: Cocaine hydrochloride was given (15 mg/kg body weight s.c.) to male Sprague-Dawley rats of 3 weeks (n = 8), 6 weeks (n = 8) and 12 weeks (n = 8) of age, daily for 28 Days. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone (T) and estrogen (E2) were assayed, and the DNA fragmentation of germ cells was determined by gel eletronphoresis. The cell cycle, apoptosis and caspase-3 activity of germ cells were tested by flow cytometry. RESULTS: After the 28-day cocaine treatment, testes weight of the 3-week-old rats, the testes and body weights of the 6-week-old rats were decreased significantly compared to those of their corresponding controls (P < 0.05). The serum level of T was decreased significantly in the 3-week-old and 6-week-old rats, and the serum level of PRL was also decreased significantly in 12-week-old rats compared to the controls (P < 0.05). In all the three cocaine-treated groups, the isolated DNA displayed a clear ladder pattern, especially in the 6-week old rats. The number of apoptosic germ cells increased significantly in 3- and 6-week-old rats treated with cocaine (P < 0.05). The caspase-3 activity in all three groups increased significantly compared to the controls (P < 0.05), especially in the 6-week-old rats. CONCLUSION: Cocaine exposure for 28 Days leads to significant damage to male gonad and apoptosis elevation in testes of rats of different ages, especially in those of 6 weeks of age. The increase in caspase-3 activity might be a key pathway related to the early stage of apoptosis as the mechanism of cocaine-induced germ cell loss.

[The specific expression profile of homeobox gene NKX3.1 mRNA and protein in prostate tissues and its relationship with primary prostate cancer].

OBJECTIVE: To determine expressions of NKX3.1 mRNA and protein in prostatic tissues and to investigate the relation between homeobox gene NKX3.1 and prostatic carcinoma. METHODS: 76 prostatic tissues (32 cancer, 12 normal prostate and 32 benign prostatic hyperplasia tissues) and 96 non-prostatic tissues were analyzed for the detection of expressions of NKX3.1 mRNA and protein by using semi-quantitative RT-PCR, Western blotting and immunohistochemical technique. RESULTS: In 76 prostatic tissues, NKX3.1 mRNA was detected in 75 specimens (98.7%), whereas in 96 non-prostatic specimens, NKX3.1 mRNA was negatively expressed in the tissues of bladder, kidney, liver, intestine, fat and skin, except for two expressed in testis and one in mammary gland. The expression ratio of NKX3.1 protein in the epithelia cells of prostate was 100%, but in testis mammary gland was 16.7%, in bladder and intestine was 8.3%, and in kidney, liver, fat and skin was 0% (P < 0.01). The total strong positive ratio of NKX3.1 protein in the epithelia cell of prostate was 94.7%, 5.3% in the stroma cell of prostate (P < 0.01), and 13.6% in benignant prostate cell, 40.6% in prostate cancer (P < 0.01), respectively. CONCLUSION: It is suggested that NKX3.1 is not only the prostate-specific homeobox gene, but is the epithelia-cell-specific gene of prostate. It may play an important role in the development of prostatic carcinoma.

[Sexual-nerve-Sparing radical cystectomy: experience with 32 cases].

OBJECTIVE: To evaluate the effect of sexual-nerve-sparing radical cystectomy. METHODS: Thirty-two male patients were treated with sexual-nerve-sparing radical cystectomy in our hospital in the past 5 years. The age of the patients ranged from 38 to 72 years, with the course of the disease ranging from 2 days to 20 years. All of them were potent preoperatively. Radical cystectomy was performed antegradely and retrogradely with the neurovascular bundle spared. RESULTS: The patients were followed up for 6 to 54 months, 3 achieved sexual activity of Grade I, 6 Grade II and 23 Grade III after the operation. The recovery time of erectile function ranged from 2 to 14 months, averaging at 4. 5 months. CONCLUSION: Whenever condition suits, sexual-nerve-sparing radical cystectomy is to be strongly recommended.